Smith Darren A, Holroyd Leo F, van Mourik Tanja, Jones Anita C
EaStCHEM School of Chemistry, The University of Edinburgh, David Brewster Road, Edinburgh, EH9 3FJ, UK.
EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
Phys Chem Chem Phys. 2016 May 25;18(21):14691-700. doi: 10.1039/c5cp07816d.
The fluorescence properties of dinucleotides incorporating 2-aminopurine (2AP) suggest that the simplest oligonucleotides adopt conformations similar to those found in duplex DNA. However, there is a lack of structural data for these systems. We report a density functional theory (DFT) study of the structures of 2AP-containing dinucleotides (deoxydinucleoside monophosphates), including full geometry optimisation of the sugar-phosphate backbone. Our DFT calculations employ the M06-2X functional for reliable treatment of dispersion interactions and include implicit aqueous solvation. Dinucleotides with 2AP in the 5'-position and each of the natural bases in the 3'-position are examined, together with the analogous 5'-adenine-containing systems. Computed structures are compared in detail with typical B-DNA base-step parameters, backbone torsional angles and sugar pucker, derived from crystallographic data. We find that 2AP-containing dinucleotides adopt structures that closely conform to B-DNA in all characteristic parameters. The structures of 2AP-containing dinucleotides closely resemble those of their adenine-containing counterparts, demonstrating the fidelity of 2AP as a mimic of the natural base. As a first step towards exploring the conformational heterogeneity of dinucleotides, we also characterise an imperfectly stacked conformation and one in which the bases are completely unstacked.
含有2-氨基嘌呤（2AP）的二核苷酸的荧光特性表明，最简单的寡核苷酸采用的构象与双链DNA中的构象相似。然而，这些系统缺乏结构数据。我们报道了一项关于含2AP的二核苷酸（脱氧二核苷单磷酸）结构的密度泛函理论（DFT）研究，包括对糖磷酸骨架进行完整的几何优化。我们的DFT计算采用M06-2X泛函来可靠地处理色散相互作用，并包括隐式水溶剂化。研究了5'-位含2AP且3'-位为各天然碱基的二核苷酸，以及类似的5'-位含腺嘌呤的系统。将计算得到的结构与从晶体学数据得出的典型B-DNA碱基步参数、骨架扭转角和糖环构象进行了详细比较。我们发现，含2AP的二核苷酸在所有特征参数上都采用了与B-DNA紧密相符的结构。含2AP的二核苷酸的结构与含腺嘌呤的对应物的结构非常相似，证明了2AP作为天然碱基模拟物的保真度。作为探索二核苷酸构象异质性的第一步，我们还对一种不完全堆积的构象和一种碱基完全未堆积的构象进行了表征。
